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Effects of tryptophan deficiency on prepulse inhibition of the acoustic startle in rats

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Abstract

Rationale

Serotonin (5-HT) plays a key role in the pathophysiology of psychotic disorders, presumably through a modulation of dopamine (DA) transmission. Reduction of 5-HT signaling has been suggested to enhance dopaminergic responses in animal models of psychosis. An intriguing naturalistic strategy to reduce 5-HT brain content is afforded by the dietary restriction to its precursor, l-tryptophan (TRP).

Objective

We investigated the impact of a TRP-deficient diet in rats on the prepulse inhibition of the startle (PPI), a measure of sensorimotor gating which is typically impaired by psychotomimetic substances.

Materials and methods

After either short-term (6 h) or long-term (14 days) TRP deprivation, rats were tested for startle reflex and PPI. Moreover, we assessed the impact of both TRP deprivation regimens on PPI reduction induced by the psychotomimetic substance d-amphetamine (AMPH).

Results

Both TRP-deficient regimens failed to significantly affect PPI responses. However, chronic, but not short-term, TRP-deficient diet induced a significant sensitization to the effects of AMPH (1.25–2.5 mg/kg, subcutaneous). The enhanced predisposition to PPI disruption elicited by prolonged TRP deprivation was completely reversed 24 h after reinstatement of TRP in the diet, as well as pretreatment with antipsychotic drugs haloperidol (0.1 mg/kg, intraperitoneal) and clozapine (5 mg/kg, intraperitoneal), which exert their therapeutic action mostly through blockade of DA D2 receptors.

Conclusions

The present results confirm and extend previous findings on the impact of serotonergic signaling in the modulation of DA transmission in schizophrenia and point to chronic TRP deprivation as a potential model of environmental manipulation that may produce a sensitization to psychotic-like symptoms induced by dopaminergic activation.

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Authors and Affiliations

  1. Department of Neuroscience “Bernard B. Brodie”, University of Cagliari, Cittadella Universitaria, S.S.554 Km 4,500, 09042, Monserrato, CA, Italy

    Marco Bortolato, Roberto Frau, Marco Orrù & Maria Collu

  2. Department of Cardiovascular and Neurological Sciences, University of Cagliari, Cagliari, Italy

    Marco Bortolato

  3. Department of Experimental Biology, University of Cagliari, Cagliari, Italy

    Giampaolo Mereu

  4. Department of Sciences Applied to Biosystems, University of Cagliari, Cagliari, Italy

    Manolo Carta, Fabio Fadda & Roberto Stancampiano

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  1. Marco Bortolato
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  2. Roberto Frau
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  3. Marco Orrù
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  4. Maria Collu
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Correspondence to Marco Bortolato.

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Fabio Fadda and Roberto Stancampiano contributed equally to the study.

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Bortolato, M., Frau, R., Orrù, M. et al. Effects of tryptophan deficiency on prepulse inhibition of the acoustic startle in rats. Psychopharmacology 198, 191–200 (2008). https://doi.org/10.1007/s00213-008-1116-9

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